methyl 2-((tert-butoxycarbonylamino)methyl)-5-fluorobenzoate | 606080-45-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-((tert-butoxycarbonylamino)methyl)-5-fluorobenzoate
• 英文别名: methyl 2-t-butyloxycarbonylaminomethyl-5-fluorobenzoate；Methyl 2-(((tert-butoxycarbonyl)amino)methyl)-5-fluorobenzoate；methyl 5-fluoro-2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoate
• CAS: 606080-45-9
• 化学式: C₁₄H₁₈FNO₄
• 分子量: 283.3
• InChiKey: CVTKTXWPQZXSOV-UHFFFAOYSA-N

物化性质

• 沸点：
  405.0±45.0 °C(Predicted)
• 密度：
  1.167±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-((tert-butoxycarbonylamino)methyl)-5-fluorobenzoate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 tert-butyl 4-fluoro-2-((5-(N-methylsulfamoyl)pentyl)carbamoyl)benzylcarbamate
  参考文献：
  名称：

  Copper-Catalyzed C–N Coupling in the Synthesis of Integrase Inhibitors of Immunodeficiency Viruses

  摘要：

  This contribution describes the total synthesis of a complex macrocyclic integrase inhibitor, a key enzyme involved in the infection process of various immunodeficiency viruses. The key transformation of the synthetic strategy was the selective C-N coupling of a sulfonamide to a heteroaryl bromide in the presence of potentially competing amide and carbamate functionalities. The transformation was accomplished with CuI catalysis using bypiridine as the ligand in the presence of base and enabled a convergent approach to the target molecule.

  DOI：

  10.1021/op400228z
• 作为产物：
  描述：

  2-氰基-5-氟苯甲酸甲酯 、 二碳酸二叔丁酯 在 镍 氢气 、 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 methyl 2-((tert-butoxycarbonylamino)methyl)-5-fluorobenzoate
  参考文献：
  名称：

  Preparation of 2-aminomethyl-5-fluorobenzamides

  摘要：

  将第七式的苯甲酰胺化合物通过将第五式的苯甲酸酯化合物与胺反应制备得到苯甲酰胺化合物VI，然后用胺去保护剂处理苯甲酰胺VI以获得苯甲酰胺VII；其中R1和R2分别独立地为H、烷基、取代烷基、环烷基、取代环烷基、芳基或取代芳基；R3为烷基、-烷基芳基或芳基；P*为氨基保护基。该制备方法的实施方式包括以下一个或多个附加步骤：通过用胺保护剂处理具有N-保护的邻氨甲基取代基的对苯甲酸酯IV，氢化邻氰基苯甲酸酯III（也称为苯腈III）以获得苯甲酸酯IV，氰化邻卤苯甲酸酯II以获得苯腈III，以及酯化邻卤苯甲酸I以获得邻卤苯甲酸酯II。第七式的苯甲酰胺化合物在HIV整合酶抑制剂的制备中作为中间体具有用途。

  公开号：

  US20040220273A1

文献信息

• HIV integrase inhibitors
  申请人：Naidu Narasimhulu B.

  公开号：US20070111984A1

  公开（公告）日：2007-05-17

  The invention encompasses a series bicyclic pyrimidinone compounds of Formula I which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

  这项发明涵盖了一系列公式I的双环嘧啶酮化合物，它们能抑制HIV整合酶，防止病毒整合到人类DNA中。这一作用使得这些化合物对治疗HIV感染和艾滋病具有用处。该发明还涵盖了用于治疗HIV感染者的药物组合物和方法。
• Preparation of 2-aminomethyl-5-fluorobenzamides
  申请人：——

  公开号：US20040220273A1

  公开（公告）日：2004-11-04

  Benzamide compounds of Formula VII are prepared by reacting a benzoate compound of Formula V with an amine to obtain a benzamide compound of Formula VI, and then treating the benzamide VI with an amine deprotecting agent to obtain the benzamide VII; wherein R 1 and R 2 are each independently H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, or substituted aryl; R 3 is alkyl, -alkylaryl, or aryl; and P* is an amino protective group. 1 Embodiments of this preparative method include one or more of the following additional steps: obtaining the benzoate V having the N-protected ortho-aminomethyl substituent by treating the corresponding benzoate IV having a free aminomethyl substituent with an amine protecting agent, hydrogenating an ortho-cyanobenzoate III (also referred to as benzonitrile III) to obtain the benzoate IV, cyanating an ortho-halobenzoate II to obtain benzonitrile III, and esterifying an ortho-halobenzoic acid I to obtain ortho-halobenzoate II. The benzamides are Formula VII are useful as intermediates in the preparation of HIV integrase inhibitors.

  将第七式的苯甲酰胺化合物通过将第五式的苯甲酸酯化合物与胺反应制备得到苯甲酰胺化合物VI，然后用胺去保护剂处理苯甲酰胺VI以获得苯甲酰胺VII；其中R1和R2分别独立地为H、烷基、取代烷基、环烷基、取代环烷基、芳基或取代芳基；R3为烷基、-烷基芳基或芳基；P*为氨基保护基。该制备方法的实施方式包括以下一个或多个附加步骤：通过用胺保护剂处理具有N-保护的邻氨甲基取代基的对苯甲酸酯IV，氢化邻氰基苯甲酸酯III（也称为苯腈III）以获得苯甲酸酯IV，氰化邻卤苯甲酸酯II以获得苯腈III，以及酯化邻卤苯甲酸I以获得邻卤苯甲酸酯II。第七式的苯甲酰胺化合物在HIV整合酶抑制剂的制备中作为中间体具有用途。
• N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides useful as hiv integrase inhibitors
  申请人：Egbertson Melissa

  公开号：US20050176955A1

  公开（公告）日：2005-08-11

  N-(Substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides are inhibitors of HIV integrase and inhibitors of HIV replication. The naphthyridine carboxamides are of Formula (I): wherein R 1 ′, R 2 ′ and R 3 ′ are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are described.

  N-(取代苯基)-8-羟基-1,6-萘啶-7-羧酰胺是HIV整合酶的抑制剂和HIV复制的抑制剂。萘啶羧酰胺的化学式为(I):其中R1'，R2'和R3'在此被定义。这些化合物在预防和治疗HIV感染以及预防、延迟发病和治疗艾滋病方面非常有用。这些化合物可以作为化合物本身或作为药物可接受的盐形式用于对抗HIV感染和艾滋病。这些化合物及其盐可以作为药物组合物中的成分，可选择与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。描述了预防、治疗或延迟艾滋病发病的方法以及预防或治疗HIV感染的方法。
• Potassium salt of an hiv integrase inhibitor
  申请人：Palucki Michael

  公开号：US20060211687A1

  公开（公告）日：2006-09-21

  A potassium salt of Compound A is disclosed, wherein Compound A is of formula (1): Compound A is an integrase inhibitor useful for preventing or treating HIV infection, for delaying the onset of AIDS, and for treating AIDS.

  本文披露了化合物A的钾盐，其中化合物A的化学式为（1）：化合物A是一种整合酶抑制剂，可用于预防或治疗HIV感染，延缓艾滋病的发作，并用于治疗艾滋病。
• N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides useful as HIV integrase inhibitors
  申请人：Merck & Co., Inc.

  公开号：US07323460B2

  公开（公告）日：2008-01-29

  N-(Substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides are inhibitors of HIV integrase and inhibitors of HIV replication. The naphthyridine carboxamides are of Formula (I): wherein R1′, R2′ and R3′ are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are described.

  N-(取代苯基)-8-羟基-1,6-萘啶-7-羧酰胺是HIV整合酶的抑制剂和HIV复制的抑制剂。萘啶羧酰胺的化合物为公式（I）：其中R1'，R2'和R3'在此定义。这些化合物在预防和治疗HIV感染以及预防、延迟发病和治疗艾滋病方面非常有用。这些化合物作为化合物本身或以药学上可接受的盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可以与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用作为制药组合物的成分。还描述了预防、治疗或延迟艾滋病发病的方法以及预防或治疗HIV感染的方法。